This invention relates to a novel monoclonal antibody (mAb) reactive with a wide variety of human leukemias and lymphomas, to a novel monoclonal antibody generated from a novel hybridoma cell line, and to methods of using the monoclonal antibody, in whole or in part, for the diagnosis and therapy of various human leukemia-lymphomas (LL).
During the last few decades, considerable improvement in the therapy of various forms of human LL has been achieved primarily because of the successful application of chemo-radiotherapy (e.g., reviewed in DeVita et al., Cancer Res. 47, 5810-5824 [1987]). However, many forms of LL are still associated with poor prognosis. These LL include low-grade NHL, prolymphocytic leukemia, B ALL, acute myelogenous leukemia, and chronic myelogenous leukemia. In this regard, there still exists a strong need for the development of a new modality for treating LL.
Recently, several mAbs directed toward LL associated antigens have been shown to be useful for diagnosis and follow-up of LL (Foon et al., Blood, 68: 1-31 [1986]). However, few, if any, anti-LL mAbs were clearly shown to be effective in the in vivo therapy (serotherapy) of LL. Therefore, the generation and characterization of new effective anti-LL mAbs are valuable.
A promising approach to the serotherapeutic utilization of anti-LL mAbs is to target LL cells by conjugating a mAb with an appropriate cytotoxic agent such as chemotherapeutic drugs, toxin subunits, or radioisotopes (reviewed in Ghose et al., J. Natl. Cancer Inst. 61: 657-676 [1978]; Vitetta et al., Science [Washington, D.C.] 238: 1098-1104 [1987]; Seon et al., New Horizons in Tumor Immunology, pp. 329-348, Amsterdam Elsevier Science Publishers [1989] and Order et al., Cancer Res. [Suppl.] 50 10115-10135 [1990]). The tumor specificity of the mAb is of paramount importance in the preparation of an effective immunoconjugate of an anti-LL mAb. In addition, a high binding of the mAb to target antigen and a relatively abundant target antigen on the cells are important. Furthermore, in most cases, the mAb needs to be effectively internalized into the target cells after binding to the cell surface antigen. However, antibody binding to the target antigen should not induce a strong down-regulation of antigen expression (Luo et al., J. Immunology, 145: 1974-1982 [1990]).